Thousands of chemicals contained in food packaging may potentially migrate into foods and result in consumer exposure. There is an increasing alarm about their potential toxicological effects since most of them lack data, while others (e.g. bisphenol A) have created significant debate because of their documented endocrine properties. This project, SafePack, aims to offer a publicly usable in silico strategy to establish rapidly and cost-efficiently the level of safety concern of packaging chemicals without animal toxicity testing. There has been already initiatives to screen packaging chemicals using in silico toxicology, but all of them use qualitative approaches, mainly mutagenicity predictions, suitable for hazard identification. However they do not provide information about hazard characterization (how much is needed for triggering a toxic effect) and even less about health risks. In toxicology, "the dose makes the poisons" and it is very important to address safety concern by balancing predicted toxicological alert with potential exposure as done in standard risk assessment. The SafePack project aims at a) fill the toxicological data gaps of large sets of packaging chemicals using computational tools to predict toxicities, b) compare predicted toxicological values with exposure to obtain Margins of Exposure (MoE), a powerful method to establish level of safety concern, c) implement the overall workflow in freely available VEGA platform to make it ready for free utilization. Thousands packaging chemicals will be compiled. A number of toxicity endpoints relevant for risk assessment will be sequentially screened using available in silico predictive models: mutagenicity, carcinogenic potency and chronic toxicity; also, endocrine activity and developmental toxicity will be covered. The quantitative predicted values will be compared to exposure estimates providing MoEs, the size of which determines the level of safety concern.

Despite improved treatment, diabetes remains a chronic disease with major health risks and heavy burden on patients and society. Serious forms are caused by depletion in pancreatic beta cells and associated loss in insulin’s homeostatic control throughout life. Their cure requires restoration of a metabolically adequate beta cell mass. Implants of beta cell grafts prepared from human pancreases have shown proof-of-principle but also the need for developing a large-scale source for therapeutic cells. Our objective is to generate a functional beta cell mass by stem cell-derived implants in diabetes patients. A combined preclinical and clinical project will search recipient and implant conditions for formation and maturation of beta cells in subcutaneous implants of device-encapsulated pancreatic endodermal cells that are derived from human embryonic stem cells (hu-ES) and manufactured for clinical studies. We collected preclinical evidence for the therapeutic potential of this implant from comparison with clinically used human beta cell grafts. State-of-the art methods and markers have been developed to investigate the biology of implants and to monitor host immune and innate reactivity. This approach helps understand the basis for metabolic outcome and identify targets for improvement. Pilot studies examine the influence of the (auto)immune status of the patients. Data will determine transition to clinical efficacy studies, or indicate the need for further laboratory development. Implants in preclinical models will guide modifications in clinical protocols, and explore the biologic properties of grafts derived from human induced pluripotent stem cell (iPSc) as can also be prepared from diabetes patients. Our consortium joins innovating cells, methods, markers and minds in a unique combination of expert clinical, academic and industry activities that need each other to make progress in an ambitious program.